Nerve probe

ABSTRACT

Systems and methods provide interface to a patient&#39;s autonomic nerves via an interior lumen wall of a blood vessel. Systems can include a probe having at least one electrode for receiving electrical signals from the interior of the lumen wall. The system can include processing components for extracting the signals from noise within the patient&#39;s body. Systems can include stimulation electrodes for providing stimulation and eliciting action potentials within the patient and destructive processes for destroying nervous function. The effect of nerve destruction on the propagation of action potentials can be effectively used as a feedback mechanism for determining the amount of nervous function destruction in the patient.

PRIORITY CLAIM

This application is a continuation of and claims priority to U.S. patentapplication Ser. No. 15/943,354, filed Apr. 2, 2018, which is acontinuation of and claims priority to U.S. patent application Ser. No.14/683,966, filed Apr. 10, 2015, now U.S. Pat. No. 9,999, 463, whichclaims the benefit of priority under 35 U.S.C. § 119(e) to U.S.Provisional Application No. 61/979,339, filed Apr. 14, 2014, all ofwhich are incorporated herein by reference in their entireties toprovide continuity of disclosure.

BACKGROUND

New medical therapies have been practiced whereby a probe such as aneedle, catheter, wire, etc., is inserted into the body to a specifiedanatomical location and destructive means are conveyed to nerves bymeans of the probe to irreversibly damage tissue in the nearby regions.The objective is to abolish nerve function in the specified anatomiclocation. The result is that abnormally functioning physiologicalprocesses can be terminated or modulated back into a normal range.Unfortunately, such medical therapies are not always successful becausethere is no means to assess that the nervous activity has beensuccessfully abolished.

An example is renal nerve ablation to relieve hypertension. Variousstudies have confirmed the relationship of renal nerve integrity withblood pressure regulation. In various renal ablation procedures, acatheter is introduced into a hypertensive patient's arterial vascularsystem and advanced into the renal artery. Renal nerves are located inthe arterial wall and in regions adjacent to the artery. Destructivemeans are delivered to the renal artery wall to an extent intended tocause destruction of nerve activity. Destructive means include energysuch as RF, ultrasound, laser or chemical agents. The objective is toabolish the renal sympathetic nerve activity. Such nerve activity is animportant factor in the creation of hypertension and abolishment of thenerve activity reduces hypertension.

Unfortunately, not all patients respond to this therapy. Renal nerveablation procedures are often ineffective and are caused by a poorprobe/ tissue interface. Accordingly, insufficient quantities ofdestructive means are delivered to the sympathetic nerve fiberstransmitting along the renal artery. One reason is that the delivery ofdestructive means to the arterial wall does not have a feedback controlmechanism to assess the destruction of the nerve activity. As aconsequence, an insufficient quantity of destructive means is deliveredand nervous activity is not abolished. Clinicians therefore require ameans of improving the probe/tissue interface, and a technology tomonitor the integrity of the nerve fibers passing through the arterialwall in order to confirm destruction of nerve activity prior toterminating therapy. Current technology for the destruction ofsympathetic nerve activity does not provide practitioners with feedbackcontrol mechanisms to detect when the desired nervous activitydestruction is accomplished. Nerve destructive means are appliedempirically without knowledge that the desired effect has been achieved.

It is known that ablation of the renal artery, with sufficient energy,is able to effect a reduction in both systolic and diastolic bloodpressure. Current methods are said to be, from an engineeringperspective, open loop; i.e., the methods used to effect renaldenervation do not employ any way of measuring, in an acute clinicalsetting, the results of applied ablation energies. It is only afterapplication of such energies and a period of time (3-12 months) that theeffects of the procedure are known.

The two major components of the autonomic nervous system (ANS) are thesympathetic and the parasympathetic nerves. The standard means formonitoring autonomic nerve activity is situations such as described isto insert very small electrodes into the nerve body or adjacent to it.The nerve activity creates an electrical signal in the electrodes whichis communicated to a monitoring means such that a clinician can assessnerve activity. This practice is called microneurography and itspractical application is by inserting the electrodes transcutaneously tothe desired anatomical location. This is not possible in the case of theablation of many autonomic nerves proximate arteries, such as the renalartery, because the arteries and nerves are located within the abdomenand cannot be accessed transcutaneously with any reliability. Thus theautonomic nerve activity cannot be assessed in a practical orefficacious manner.

The autonomic nervous system is responsible for regulating thephysiological processes of circulation, digestion, metabolism,reproduction, and respiration among others. The sympathetic nerves andparasympathetic nerves most often accompany the blood vessels supplyingthe body organs which they regulate. Examples of such include but arenot limited to the following: (1) Nerves regulating liver functionaccompany the hepatic artery and the portal vein. (2) Nerves regulatingthe stomach accompany the gastroduodenal, the right gastroepiploicartery, and the left gastric artery. (3) Nerves regulating the spleenaccompany the lineal artery. (4) Nerves from the superior mesentericplexus accompany the superior mesenteric artery, where both the arteryand the nerves branch to the pancreas, small intestine, and largeintestine. (5) Nerves of the inferior mesenteric plexus accompany theinferior mesenteric artery and branch with the artery to supply thelarge intestine, the colon, and the rectum.

When monitoring ANS activity, one must generally differentiate betweenthe electrical signals generated by the ANS and those generated bymuscle activity, which is commonly called EMG. EMG signals possessamplitudes several orders of magnitude larger than compared to those ofthe ANS. Probes possessing electrodes have been used to assess the EMGof the heart, stomach, intestines, and other muscles of the body. Suchprobes and their means and methods for detecting and analyzing theelectric signals are not suitable for use with signals generated by theANS.

Deficiencies in the use of existing therapeutic protocols in denervationof autonomic nerves proximate arteries include: 1. The inability todetermine the appropriate lesion sites along the artery that correspondto the track of nerves; 2. The inability to verify that the destructivedevices are appropriately positioned on the arterial wall, normalizingthe tissue/device interface and enabling energy transfer through thevessel wail, and 3. Inability to provide feedback to the clinicianintraoperatively to describe lesion completeness or the integrity of theaffected nerve fibers. As a consequence, current autonomic nerveablation procedures are performed in a ‘blinded’ fashion; the clinicianperforming the procedure does not know where the nerves are located; andfurther, whether the nerves have truly been ablated. Instead, surrogatessuch as catecholamine spillover into the circulating blood have beenused to attempt to evaluate the termination of autonomic nerve activitysuch as renal sympathetic nerve activity (RSNA). It is entirely likelythat this deficiency could largely be responsible for the currentquestionable data coming from clinical trials in the US. Therefore, asystem designed to indicate with precision, and in real time, whetherablation was successful is urgently needed.

SUMMARY

Aspects of the disclosure are generally toward systems and methods forinterfacing with the autonomic nervous system of a patient via aninterior wall of a blood vessel. In some embodiments, a system includesa probe having at least one electrode capable of detecting electricalsignals from an interior wall of a blood vessel. The system can includean electrical control unit (ECU) in electrical communication with theprobe and capable of receiving an electrical signal from the at leastone electrode of the probe. The ECU can process the received signal toproduct an output signal, and present information including informationabout the output signal, the received signal, or processing information.Such systems can be used, for example, in diagnostic procedures forassessing the status of a patient's nervous activity proximate the bloodvessel.

In some examples, the system can include a stimulation electrode forproviding an electrical stimulus into the interior wall of the bloodvessel. The electrical stimulus can be sufficient to provoke an elicitedpotential in the patient's nerves. The system can receive and process asignal including the elicited potential. Embodiments of the system canfurther perform a nerve destruction process to destroy nervous tissue orfunction proximate the blood vessel. The system can evoke and detectelicited potentials before and after the nerve destruction process andcompare the detected potentials to determine the effective amount ofdestruction that has taken place.

In further examples, nerve destruction processes can be performed afterat least one diagnostic procedure. For example, a diagnostic procedurecan be performed to determine the level of nervous activity in nervesproximate a patient's blood vessel. The level of activity can beanalyzed to determine whether or not a nerve destruction process islikely to be effective therapy for a patient. If so, nerve destructionprocesses can be performed.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1D are exemplary probe designs according to variousembodiments.

FIG. 2 is a schematic diagram of an exemplary system for interfacingwith a patient's arterial nerves.

FIG. 3 is a process-flow diagram illustrating an exemplary nerveanalysis and destruction process.

FIG. 4 is an exemplary plot representative of an electrical stimulus andan elicited potential detected in a patient's nervous system.

FIG. 5A-5C are a series of exemplary plots showing the effect of nervedestruction on elicited potentials in a patient's nervous system.

FIG. 6 is an exemplary probe design for inserting into a patient'sartery.

FIG. 7 is a process-flow diagram illustrating an exemplary diagnosticprocess.

FIG. 8 is an exemplary plot of electrical signals detected in apatient's nervous system.

DETAILED DESCRIPTION

The following detailed description is exemplary in nature and is notintended to limit the scope, applicability, or configuration of theinvention in any way. Rather, the following description provides somepractical illustrations for implementing various embodiments of thepresent invention. Examples of constructions, materials, dimensions, andmanufacturing processes are provided for selected elements, and allother elements employ that which is known to those of ordinary skill inthe field of the invention. Those skilled in the art will recognize thatmany of the noted examples have a variety of suitable alternatives. Somesuch alternatives or variations may be more fully appreciated withregard to U.S. patent application Ser. No. 13/796,944, filed on Mar. 12,2013, now U.S. Pat. No. 9,439,598, which is hereby incorporated byreference in its entirety.

This invention enables the real-time assessment of sympathetic andparasympathetic nerve activity by comparing stimulus-elicited potentialsbefore and after the delivery of a destructive means to the selectednerves. Electrical stimulation is delivered to the arterial wall in afashion to reliably elicit maximal nerve activity. The resultantactivity transmits distally past a destructive means and towards asystem used to record the elicited activity. Comparisons of the neuralbursts elicited before and after ablation can be used to indicate thecontinuity and integrity of the interposed nerve fibers.

Various methods of eliciting and assessing autonomic nerve activity caninclude inserting a probe containing both therapeutic means forperforming destructive processes and stimulating and recordingelectrodes for eliciting and assessing nervous activity into thepatient's body to a desired anatomic location. In some examples, theprobe can be inserted through a blood vessel of the patient in order toelicit and assess nerve activity associated with nerves proximate thatblood vessel. In still further embodiments, the probe is inserted intoan artery into an organ, for example, those described above.

In some embodiments, a clinician may first use the electrodes in amonitoring fashion to establish baseline nervous system function.Alternatively, the clinician may first use the electrodes in astimulation mode to initiate a nervous activity response which can bemeasured by the electrodes in a monitoring mode. The clinician may thenapply destructive means to the tissue, such as described in U.S. patentaplication Ser. No. 13/796,944, now U.S. Pat. No. 9,439,598. Theclinician may next apply the cycle of nerve stimulation and monitoringto assess whether or not the nerve activity has been abolished. Ifnervous activity still exists, then the device may indicate to theclinician a value indicative of nerve destruction completeness. Forexample, the device may estimate an amount of nerve destruction based onthe magnitude of detected nervous activity compared to the magnitude ofdetected nervous activity prior to nerve destruction. The estimatedamount of nerve destruction may be in the form of a percentage, forexample. At this time, the clinician may assess the level of denervationor destruction and stop, or proceed to deliver another application ofdestructive means for a more complete lesion. The cycle of application,stimulation, and monitoring may be repeated until nervous activity isabolished, and/or the clinician has reached an intended level ofdenervation.

Various systems and devices can be used for performing such processes.Some embodiments of the invention comprise a probe for inserting intothe patient, for example into a patient's renal artery or any otherappropriate lumen in the patient's vasculature. The probe can include aplurality of electrodes directing an electrical stimulus into thepatient's body, and for detecting electrical signals elicited within thepatient. In various embodiments, electrodes can be arranged along theaxis of the probe, around the circumference of the probe, or in anyother appropriate arrangement for carrying out various methods accordingto the present invention. Various electrode configurations are describedin U.S. patent application Ser. No. 13/796,944, now U.S. Pat. No.9,439,598. In some configurations, the probe and electrodes are suchthat, when the probe is inserted into a patent's artery, the electrodesare placed in contact with the artery lumen wall. Such contact permitsthe application of electrical stimulation from the electrodes to thewall, and the detection of electrical signals from the wall via theelectrodes. Various exemplary electrode configurations including avarying number of electrodes are shown in FIGS. 1A-1D and describedbelow.

In some embodiments, such as that shown in FIG. 1A, the probe comprisesa first electrode and a second electrode. Such a system can furtherinclude a third electrode applied on the patient's skin (not shown). Afirst electrode mounted on the probe can be used to deliver anelectrical stimulus to the surrounding tissue in a monopolar fashion,with the electrode placed on the person's skin being used as the returnelectrode during stimulation. Distal to the stimulating electrode, thesecond electrode can be used to record elicited bursts of autonomicactivity resulting from the stimulus from the first electrode to thethird electrode. In some embodiments, during a recording session, theelectrode placed on the skin can be used as the indifferent electrode ofthe electrode pair.

An alternate configuration, such as is shown in FIG. 1B, can includethree electrodes on the probe. In such a configuration ,two electrodeswould be dedicated to stimulation and the third would be paired with theexternal electrode for monitoring.

Another alternative configuration, shown in FIG. 1C, can include 4electrodes on a single probe: one stimulating electrode, and threerecording electrodes. The three recording electrodes can be setup toinclude an active electrode, an inactive electrode and a commonelectrode, for example. The one stimulating electrode can operate in amonopolar fashion, wherein an external surface electrode positioned onthe patient's skin can serve as a return electrode. Alternatively, twoelectrodes on the probe can be used as stimulating electrodes and canoperate in a bipolar fashion, while the remaining two electrodes couldbe used for recording/detecting signals, such as in the form of anactive and inactive pair.

Still another alternative configuration, such as is shown in FIG. 1D,can include 5 electrodes on a single probe: two stimulating electrodesto deliver stimulation in a bipolar fashion, and three recordingelectrodes, for example active, inactive and common electrodes. Ingeneral, any number of electrodes can be used for any number ofpurposes, such as delivering stimulation in a monopolar or bipolarfashion, recording/detecting electrical signals, or measuring any otherelectrical parameter that might be desired (e.g., resistance,capacitance, etc.). In various embodiments, properties of the recordingelectrodes can be adjusted to best receive action potentials or othersignals passing along the arterial wall. For instance, in some examples,the impedance, separation distance, and size and geometry of therecording electrodes can be adjusted.

It will be appreciated that, while various examples are shown in FIGS.1A-1D, suitable probes can include any number of electrodes forperforming a variety of functions. For instance, further embodiments ofa probe can include three or more stimulating electrodes. In some suchexamples, stimulating electrodes can include a pair of electrodes forbipolar stimulation as well as a reference electrode or a blockingelectrode, as will be described below. In other embodiments, additionalelectrodes (e.g., third electrode, fourth electrode, etc.) can be usedas alternative electrodes in the event that a first pair of electrodesdoes not make adequate electrical contact with the arterial wall of thepatient. In such embodiments, alternate stimulating electrodes can beused to provide unipolar or bipolar stimulation to the patient'sarterial wall.

In some embodiments, means for applying destructive energy to nerveswithin or proximate the probe are provided. Such destructive means caninclude, for example, radiofrequency (RF), ultrasonic, microwave, laseror chemical agents. In some embodiments, the destructive means areapplied between the stimulating electrode(s) and the recordingelectrode(s). Accordingly, the stimulating electrode(s) applies astimulus to the arterial wall and elicits a potential within the patientthat travels at some propagation velocity (e.g., between approximately0.2 m/s and approximately 8 m/s) toward the recording electrode(s),where it can be detected. When a destructive process is performedbetween the stimulating and recording electrode(s), subsequent elicitedpotentials traveling from proximate the stimulating electrode(s) towardthe recording electrode(s) must traverse the region of nerves to whichdestructive means has been applied. Accordingly, any effect that thedestruction process has on the elicited potential can be observed at therecording electrode(s).

As shown in FIGS. 1A-1D, the stimulating electrodes are shown on theleft side of the probe, while the recording electrodes are shown on theright side. In some embodiments, the probe is inserted into an arterysuch that the recording electrodes are more proximate an organassociated with the artery than are the stimulating electrodes, such asshown in FIG. 2 . However, in alternative embodiments, the stimulatingelectrodes can be more proximate the organ than the recordingelectrodes.

Any number of electrodes on the probe can generally be in electricalcommunication with electrical circuitry for applying electrical signals(e.g., stimulation signals) stimulating electrodes or for receivingand/or processing signals from the electrodes. In some examples,circuitry can include various components, such as a processor andoperational amplifier with capacitance control in electricalcommunication with an active recording electrode on the probe forprocessing received electrical signals. In some embodiments, the activeelectrode can possess high impedance. Additionally or alternatively, theactive electrode can be a part of an active electrode circuit (e.g., anactive electrode in communication with circuitry such as amplifier,processor, etc.), which can itself be configured to have a high inputimpedance. This design can block electrical noise generated by thevarious sources inherent to the intra vascular space, such as blood flowor vascular muscular contraction from being amplified. In addition, suchcircuitry can limit the detection of nerve firing to a selective regionwithin the vessel's wall. In some configurations, the amount ofimpedance and applied electrical signal can be dependent on the size andnumber of recording electrodes, as the interference effects areproportional to the total surface area of the electrode(s) used. Invarious embodiments, impedance loading can be positioned prior to anamplifier or can be incorporated into the amplifier design.

In some embodiments, the probe and electrical circuitry can be a part ofa system for stimulating, monitoring, and destructing nervous tissue. Insome such systems, the electrical circuitry can be a part of orotherwise in electrical communication with an electronic control unit(ECU). In various embodiments, the ECU can include a signal emittingportion and/or a signal receiving portions, and can be configured toemit electrical signals to and/or to receive electrical signals from theprobe, respectively.

FIG. 2 is a system diagram of an exemplary system for interfacing with apatient's arterial nerves. As shown, the system 200 of FIG. 2 includesan ECU 202 in electrical communication with a probe 240 inserted in anartery 250 of a patient. The ECU 202 includes a stimulator 206 havingelectrodes 208 in electrical communication with stimulating electrodes242 on the probe 240. The stimulator 206 can emit electrical signals tothe stimulating electrodes 242 via electrodes 208. When emitting asignal to the probe, the signal can have specific voltage, amperage,duration, and/or frequency of application that will cause nenle cellactivation. In an exemplary embodiment, the electrodes 208 can includean anode and a cathode. Further, in some such embodiments, the cathodecan be electrically coupled to a stimulating electrode 242 that islocated distally from a stimulating electrode 242 that is electricallycoupled to the anode. It will be appreciated that, in such an example,stimulating electrodes 242 can similarly be referred to as the anode andcathode due to the respective electrical connection between stimulatingelectrodes 242 and electrodes 208. That is, electrodes 242 may includean anode and a cathode based on functional operation associated withrespectively connected electrodes 208. Thus, in some examples, the probe240 includes an anode and a cathode for applying a stimulation signal tothe arterial wall. In some such examples, the cathode can be locateddistally with respect to the anode.

Upon receiving the signal, the stimulating electrodes of the probe canapply electrical energy to a patient's nerves through the arterial wallbased on the received signal. The stimulus can have any of a variety ofknown waveforms, such as a sinusoid, a square wave form or a triangularwave form, as taught, for example, in the paper “Selective activation ofperipheral nerve fiber groups of different diameter by triangular shapedstimulus pulses,” by Accornero (Journal of Physiology. 1 977 December;273(3): 539-560). In various examples, the stimulation can be appliedfor durations between approximately 0.05 ms and approximately 2 ms. Suchsignals can be applied through a single, unipolar electrode or a bipolarelectrode, for example, as described with regard to the various probeconfigurations of FIGS. 1A-1D. In some examples, stimulation signals canbe applied via a bipolar electrode with “anodal blocking,” as will bedescribed below.

The probe 240 includes recording electrodes 244, in the illustratedembodiment positioned distally from stimulating electrodes 242. Therecording electrodes 244 can be configured to detect electrical signalsin the patient's nerves at a location separate from the stimulatingelectrodes 242. For example, the recording electrodes 244 can be used todetect an elicited potential caused by a stimulus from the stimulatingelectrodes 242 and propagating toward the organ.

In some configurations, the stimulation of nerves to evoke an elicitedpotential can cause such a potential to propagate in every directionalong the nerve fibers. In some situations, it can be undesirable forsuch a potential to propagate unnecessarily through the nerve forpatient safety and/or desired signal isolation purposes. In someconfigurations, the propagation of elicited action potentials can be“blocked” by applying an electrical signal to a portion of the nerve.Accordingly, in some embodiments, a probe or additional component caninclude electrodes configured to reduce or eliminate an elicitedpotential from propagating undesirably. For example, with reference toFIG. 2 , the probe 240 can include a third stimulating electrode (notshown) further from the organ along the arterial wall than the first andsecond stimulating electrodes 242. During the application of astimulation signal, a blocking stimulation pulse can be applied via thethird electrode to prevent elicited action potentials from travellingproximally along the patient's nerves while permitting the actionpotential to propagate toward the recording electrodes 244.

In some embodiments, the ECU 202 can digitally sample the signal on therecording electrode(s) 244 to receive the electrical signal from theprobe 240. In alternate embodiments, the signal can be recorded as ananalog signal. When receiving an electrical signal from the probe 240,the ECU 202 can perform filtering and/or other processing steps on thesignal. Generally, such steps can be performed to discriminate thesignal from the probe from any background noise within the patient'svasculature such that the resulting output is predominantly the signalfrom nerve cell activation. In some instances, the ECU 202 can modulatethe electrical impedance of the signal receiving portion in order toaccommodate the electrical properties and spatial separation of theelectrodes mounted on the probe in a manner to achieve the highestfidelity, selectively and resolution for the signal received. Forexample, electrode size, separation, and conductivity properties canimpact the field strength at the electrode/tissue interface.

Additionally or alternatively, the ECO 202 can comprise a headstageand/or an amplifier to perform any of offsetting, filtering, and/oramplifying the signal received from the probe. In some examples, aheadstage applies a DC offset to the signal and performs a filteringstep. In some such systems, the filtering can comprise applying notchand/or band-pass filters to suppress particular undesired signals havinga particular frequency content or to let pass desired signals having aparticular frequency content. An amplifier can be used to amplify theentire signal uniformly or can be used to amplify certain portions ofthe signal more than others. For example, in some configurations, theamplifier can be configured to provide an adjustable capacitance of therecording electrode, changing the frequency dependence of signal pick-upand amplification. In some embodiments, properties of the amplifier,such as capacitance, can be adjusted to change amplification properties,such as the resonant frequency, of the amplifier.

In the illustrated embodiment of FIG. 2 , the ECU 202 includes anamplifier 212 in communication with the recording electrodes 244 of theprobe 240 in order to receive electrical signals therefrom. Theamplifier 212 can include any appropriate amplifier for amplifyingdesired signals or attenuating undesired signals. In some examples, theamplifier has a high common-mode rejection ratio (CMRR) for eliminatingor substantially attenuating undesired signals present in each at eachof the recording electrodes 244. In the illustrated embodiment, theamplifier 212 is electrically coupled to tissue 260 of the patient forproviding a reference signal to the amplifier. In some embodiments,amplifier 212 can be adjusted as described above, for example, via anadjustable capacitance or other attributes of the amplifier.

In the exemplary system 200 of FIG. 2 , the ECU 202 further includes afilter 214 for enhancing the desired signal in the signal received fromrecording electrodes 244. As described, the filter 214 can include aband-pass filter, a notch filter, or any other appropriate filter toisolate desired signals from the received signals. Similar to theamplifier 212 discussed above, in some embodiments, various propertiesof the filter 214 can be adjusted to manipulate its filteringcharacteristics. For example, the filter may include an adjustablecapacitance or other parameter to adjust its frequency response.

At least one of amplification and filtering of the signal received atthe recording electrodes 244 can allow for extraction of the desiredsignal at 216. In some embodiments, extraction 216 comprises at leastone additional processing step to isolate desired signals from thesignal received at recording electrodes 244, such as preparing thesignal for output at 218. In some embodiments, the functionalities ofany combination of amplifier 212, filter 214, and extraction 216 may becombined into a single entity. For instance, the amplifier 212 may actto filter undesired frequency content from the signal without requiringadditional filtering at a separate filter.

In some embodiments, the ECU 202 can record emitted stimuli and/orreceived signals. Such data can be subsequently stored in permanent ortemporary memory 220. The ECU 202 can comprise such memory 220 or canotherwise be in communication with external memory (not shown). Thus,the ECU 202 can be configured to emit stimulus pulses to electrodes ofthe probe, record such pulses in a memory, receive signals from theprobe, and also record such received signal data. While shown in FIG. 2as being a part of the processor, it will be appreciated that the memoryin or associated with the ECU 202 can be internal or external to anypart of the ECU 202 or the ECU 202 itself.

The ECU 202 or separate external processor can further performcalculations on the stored data to determine characteristics of signalseither emitted or received via the probe. For example, in variousembodiments, the ECU 202 can determine any of the amplitude, duration,or timing of occurrence of the received or emitted signals. The ECU 202can further determine the relationship between the received signal andthe emitted stimulus signal, such as a temporal relationshiptherebetween. In some embodiments, the ECU 202 performs signal averagingon the signal data received from the probe. Such averaging can act toreduce random temporal noise in the data while strengthening the datacorresponding to any elicited potentials received by the probe. Anexemplary data collection procedure is outlined below:

-   -   1. Generate a stimulus pulse    -   2. Sample or record data from the receiving over a time period        of interest; stop sampling or recording after period of interest        (e.g., after any elicited potential might be detected)    -   3. Repeat steps 1 and 2; add the resulting samples to those        already sampled    -   4. Repeat steps 1 through 3 as needed        Averaging as such can result in a signal in which temporally        random noise is generally averaged out and the signal present in        each recorded data set, such as elicited potentials, will remain        high. In some embodiments, each iteration of the process can        include a synchronization step so that each acquired data set        can be temporally registered to facilitate averaging the data.        That is, events that occur consistently at the same time during        each iteration may be detected, while temporally random        artifacts (e.g., noise) can be reduced. In general, the signal        to noise ratio resulting in such averaging will improve by the        square root of the number of samples averaged in order to create        the averaged data set.

The ECU 202 can further present information regarding any or all of theapplied stimulus, the signal, and the results of any calculations to auser of the system, e.g., via output 218. For example, the ECU 202 cangenerate a graphical display providing one or more graphs of signalstrength vs. time representing the stimulus and/or the received signal.FIG. 4 is an exemplary plot of signal strength vs. time illustrating astimulus signal 400 and an associated elicited potential 402. Time stamp0 is indicative of the triggering of the stimulus signal 400 while stamp1 represents the onset of the elicited potential. In alternativeembodiments, the ECU 202 can present information representative of suchsignals to the user via an audio alert or any other appropriate methodof communication.

In some embodiments, the ECU 202 can include a controller 222 incommunication with one or both of stimulator 206 and signal processor210. The controller 222 can be configured to cause stimulator 206 toapply a stimulation signal to the probe 240. Additionally oralternatively, the controller 222 can be configured to analyze signalsreceived and/or output by the signal processor 210. In some embodiments,the controller 222 can act to control the timing of applying thestimulation signal from stimulator 206 and the timing of receivingsignals by the signal processor 210.

Exemplary electrical control units have been described. In variousembodiments, the ECU 202 can emit stimulus pulses to the probe, receivesignals from the probe, perform calculations on the emitted and/orreceived signals, and present the signals and/or results of suchcalculations to a user. In some embodiments, the ECU 202 can compriseseparate modules for emitting, receiving, calculating, and providingresults of calculations. Additionally or alternatively, thefunctionality of controller 222 can be integrated into the ECU 202 asshown, or can be separate from and in communication with the ECU.

In some embodiments, the ECU 202 can include a switching networkconfigured to interchange which of electrodes 242, 244 of the probe arecoupled to which portions of the ECU. For instance, in some examples,the ECU 202 as shown in FIG. 2 can be adjusted so that the stimulator206 is in electrical communication with electrodes 244 of the probe andthe signal processor 210 is in electrical communication with electrodes242 of the probe. Additionally or alternatively, the ECU 202 includesinputs for receiving connectors electrically coupling the ECU 202 to theelectrodes (242, 244) of the probe 240. In some such embodiments, a usercan manually switch which inputs receive connections to which electrodesof the probe 240. Such configurability allows for a system operator toadjust the direction of propagation of the elicited potential asdesired.

Some aspects of the invention include methods of using systems such asthose described above. An exemplary method is illustrated in FIG. 3 .During use, according to some embodiments, a probe is insertedpercutaneously into the arterial vasculature and advanced into an artery(302) such that the electrodes are placed in contact with the arteriallumen wall. Any appropriate probe can be used, such as exemplary probesdescribed above. Additionally, while the method of FIG. 3 is generallydirected toward interfacing with an arterial wall, similar methods canbe employed in other blood vessels. A stimulus can be emitted into thearterial lumen wail via the probe (304), and the resulting signal (e.g.,elicited signal or action potential) can be detected via the probe andrecorded to the ECU. Such a measurement can be set as a baselinemeasurement (306), since no destruction to the nerves has yet beenapplied. The recorded baseline signal can be stored in a memory in thesystem.

After recording a baseline measurement, a nerve destruction process canbe applied (308) to the nerves within or proximate the artery. Amongvarious embodiments, the nerve destruction means can be applied (i)through the artery lumen wall (310) (e.g., for the purposes ofterminating nerve activity) or (ii) through a probe inserted into thepatient's abdomen to a position in proximity to the artery (312) (e.g.,for the purposes of terminating nerve activity). The destruction processcan be ceased (314) after an amount of time, and a stimulus can onceagain be emitted via the probe (316) and the resulting elicited signalcan be detected (318) via the probe.

The detected and recorded elicited signal can be stored in memory and/orcompared to the baseline signal (320) previously stored. Based on thecomparison, a relative amount of nerve destruction performed by thedestructive means can be determined. In some embodiments, the comparisonis calculated automatically and a relative amount of destruction iscommunicated to a user. A user can then determine (322) whetheradditional destruction is appropriate, or if sufficient destruction hasbeen performed. Alternatively, in some configurations, the determinationcan be automated. That is, if the controller 222 (as a part of orseparate from the ECU 202) can determine whether or not a sufficientamount of destruction has been performed based on an automatedcomparison. For example, the controller 222 can determine if thecomparison satisfies a predetermined condition, the predeterminedcondition indicating a sufficient amount of destruction has beenperformed.

Satisfying the predetermined condition can include, in various examples,a reduction of the magnitude of the elicited potential by apredetermined percentage or absolute amount, or a complete eliminationof the elicited potential. In such automated embodiments, if it isdetermined (322) that insufficient destruction has taken place (e.g.,the predetermined condition is not met), the controller 222 can causethe destructive means to perform additional destructive processes (308)to the patient's nerves. In other embodiments, a user can manually applyadditional destructive processes (308) of insufficient destruction isdetected. If sufficient destruction has been performed (e.g., thepredetermined condition is met), then the destruction process iscomplete (324).

In general, this process can be repeated (aside from reacquiring abaseline measurement) until it has been determined that sufficientdestruction has been performed. That is, when nerve activity is reducedto an acceptable level. Then, the process is terminated and the probecan be withdrawn from the patient's body (324). FIGS. 5A-5C show theprogression of elicited potentials in arterial nerves in response to astimulus pulse as the relative amount of nerve destruction increases.FIG. 5A is a plot showing a stimulus signal 500 a and a detectedelicited response 502 a before performing a destructive operation on thearterial nerves. In some examples, FIG. 5A can represent a baselinemeasurement. FIG. 5B illustrates a stimulus signal 500 b and a detectedelicited response 502 b. As can be seen, the elicited response 502 b issignificantly smaller than elicited baseline response 502 a, indicatingthat significant destruction of arterial nerves has been performed. FIG.5C illustrates a stimulus signal 500 c and a detected elicited response502 c after still more arterial nerve destruction has been performed. Ascan be seen, the elicited response 502 c is much smaller than that ofeither the elicited baseline response 502 a or the response 502 b, andis almost non-existent. This implies that further, or possibly complete,arterial nerve destruction has taken place.

During such stimulating, detecting, and destruction procedures, manyfactors can be considered and/or manipulated to improve systemperformance. Several factors can be manipulated or taken into accountwhile stimulating nerves to elicit a response, including:

(a) Stimulus Strength—In general, the stimulus must be of a sufficientstrength (voltage) to induce an elicited potential. In some embodiments,the stimulus can be of sufficient strength such that most of the nervesalong the artery are stimulated. In some situations, such as with therenal artery, many nerves are known to run along the outside of theartery, which may require a stimulus from a probe inside the artery tobe sufficiently large for eliciting action potentials in the nerves. Insome examples, probes can be configured to provide stimulus signalsbased on a desired level of current (e.g., in a constant current mode ofoperation), for example, between approximately 1 mA and approximately 25mA, while providing whatever voltage is necessary for such currents, insome cases up to or above 100 V. In other examples, stimulations arebased only on a desired voltage (e.g., in a constant voltage mode ofoperation), such as approximately 1 V, or range of voltages, such asbetween 0. 1 V and 1 V, between 1 V and 10 V, etc.

(b) Electrode Separation—In general, for any given voltage, the closerthe electrodes are, the stronger the resulting electric field gradient.However, electrodes spaced too close together can result in a shortcircuit along the tissue itself such that the current is shunted and avoltage gradient is not allowed to develop. In some embodiments,electrodes are separated by approximately 1-3 mm. In some examples,electrode spacing can be designed based on expected action potentialmagnitude, duration, and/or propagation velocity.

(c) Pulse Width—To elicit such potentials, the pulse often will beapplied for a sufficient duration such that the voltage gradientdeveloped by the stimulus pulse has enough time to effect an action(elicited) potential, but not so long as keep the nerves in a constantstate of depolarization. In some embodiments, pulse widths can bebetween 50 to 100 μs; in other systems, pulse widths of approximately1-10 ms can be used.

(d) Frequency—Finally, the frequency or repetition rate of the stimulusneeds to be considered. In some embodiments, a frequency that is toofast can exhaust the nerve while a frequency that is too slow canunnecessarily delay the process. In various embodiments, frequencieswithin approximately 5-40 Hz can be used.

In addition to considerations of the nerve stimulation pulses, someparameters of the system are configured to maximally elicit bursts ofautonomic activity via electrodes placed within the arterial lumen, aswell as to enable sufficient detection of autonomic activity. Forexample, in some embodiments, parameters such as stimulation type,delivery fashion, pulse frequency, pulse duration, phase duration,current intensity, pulse period and pulse train of the electricalstimulation can be selected to have a maximum effect on elicitingautonomic neural activity and be amenable to recording the elicit burstsnearby. In some examples, electrodes can be spaced apart and/or sizedaccording to applied stimulation signals in order to maximize the effectof the applied stimulation. For example, the electrodes can be spacedaccording to the propagation velocity and/or stimulation pulse width sothat the entire duration of a desired pulse shape is used forstimulation purposes between the anode and the cathode.

Further, in some embodiments, various aspects of recording electrodescan be configured to better receive or distinguish elicited potential.For example, in some embodiments, the size of the recording electrodescan be selected based on at least one of the propagation velocity ofelicited potentials in the patient's nerves and the pulse width of theelicited potentials. In some embodiments, the recording electrodes havea width that is approximately the same as the pulse width of theelicited potential. In further embodiments, the recording electrodeshave a width that is smaller than the pulse width of the elicitedpotential. In general, a narrow electrode can minimize the amount ofnoise present at the surface of electrode simultaneously with theelicited potential.

As previously discussed, elicited potentials in autonomic nerves aregenerally small and are often difficult to detect. Further, the positionof autonomic nerves proximate an arterial lumen can make detection ofelicited potentials from within the artery difficult. For example, renalartery nerves lie longitudinally along the renal artery and arecircumferentially all around the arterial wall as well as outside therenal artery lumen. As such, detection of elicited potentials by anindwelling probe is made difficult both by the barrier presented by thearterial wall itself as well as the distance from the sensing electrodesto the nerves. Thus, it is important to be able to both detect anddistinguish such signals from other noise in the patient and system.

One process to enhance the detection of elicited potentials involvesexpecting any such potentials to be present at a certain time. That is,a known action potential propagation/conduction velocity and electrodespacing allows for creating a temporal window in which the elicitedpotential can be predicted to arrive at the recording electrode.Accordingly, methods according to the present invention can includereceiving elicited signals via the probe within a predetermined timewindow. For example, with respect to FIGS. 5A-5C, numeral 0 representsthe time at which the stimulus potential is applied, while numerals 1and 2 represent the start and end times in which an elicited potentialis expected based on the electrode spacing and the elicited potentialpropagation velocity. As shown, the detection elicited potentials aregenerally present within the defined temporal window. Detecting nervesignals within only a predefined temporal window can help prevent thesystem from receiving noise or other artifacts not associated withelicited potentials and falsely relating them to such potentials.

Additionally or alternatively, various steps can be employed to isolatethe detection of elicited potentials from detection of the stimulationsignal at the recording electrodes. In general, the stimulation pulsewill reach the recording electrodes before the elicited potentialarrives. This is because the elicited potential propagates by adifferent mechanism than the stimulation pulse. While the stimulationpulse propagates toward the recording electrodes due to electricalconduction through body tissues and fluids, elicited potentialspropagate along axons via a sequential cell membrane process. Suchpropagation occurs having a velocity between approximately 0.2 m/s andapproximately 200 m/s, which is comparatively slower than thestimulation pulse. Thus, in some instances, the recording electrodes canbe blanked for a period of time following the application of thesimulation pulse, allowing the stimulation pulse to effectively pass bythe recording electrodes without being recorded. Monitoring by therecording electrodes can be resumed after blanking in time to receivethe elicited potential following the stimulation pulse.

In some embodiments, the probe can be configured to allow for a maximumseparation between the simulating electrode(s) and the recordingelectrode(s). Such a configuration results in a greater temporalseparation of the stimulation pulse and the elicited potential at therecording electrodes when compared to more closely-spaced electrodes. Insome examples, the practical distance between the stimulatingelectrode(s) and the recording electrode(s) is limited by the length ofthe artery in which the probe is inserted for operation. Thus, in someembodiments, the probe comprises an adjustable distance between thestimulating electrode(s) and the recording electrode(s) in order toallow for the distance between the sets of electrodes to be maximizedwhile allowing the probe to adequately fit within the artery of thepatient.

FIG. 6 is an exemplary probe configured for adjustable separation of thestimulating and recording electrode(s). As shown, stimulating electrodes642 are present on a first portion 632 of the probe 640, while recordingelectrodes 644 are present on a second portion 634 of the probe 640. Inthe illustrated embodiment, the second portion 634 is located distallyfrom the first portion 632 in a patient's artery, for example, toward anorgan. The second portion 634 can be configured to translate relative tofirst portion 632, allowing for the adjustment of the probe length andthe separation between the stimulation 642 and recording 644 electrodes.In some examples, translation of the second portion 634 relative to thefirst portion 632 is achieved by a telescoping configuration between thefirst 632 and second 634 portions of the probe 640.

As generally discussed previously, various processing steps can beperformed by an ECU or other processor to further distinguish elicitedpotentials from other signals. As shown in the schematic diagram in FIG.2 , the ECU can include a signal processor comprising an amplifier,filter, and other signal extraction tools. The amplifier can comprise acommon-mode rejection amplifier in order to emphasize an elicited signalover the background noise of the artery. In some embodiments, theamplifier comprises a common-mode rejection ratio (CMRR) ofapproximately 100 dB or more. A band-pass filter can be used toattenuate signals not within an expected frequency band indicative ofelicited potentials. Additionally or alternatively, a band-reject filtercan be used to specifically attenuate expected noise at an expectedfrequency. For example, a band-reject filter centered aroundapproximately 60 Hz might be used. Various other signal processing andextraction techniques can similarly be employed, such as the averagingprocesses herein described.

In some embodiments, various characteristics (e.g., capacitance,resistance, etc.) of components such as the electrodes, circuitry, orparts of the ECU 202, such as an amplifier or filter, can be adjustedeither automatically or manually. For example, in some systems, thecapacitance of a filter or amplifier can be adjusted to tune bandwidthsor resonant frequencies of such components to better extract signalsrepresentative of elicited potentials. In some processes, a user orcontroller 222 can adjust such values and observe the response to suchadjustments in order to optimize system operation. That is, in someembodiments, such values are manually adjustable, and a user can adjustsuch values while observing signal detection performance. In somesituations, specific probe types have known properties that affect thestimulation or detection of elicited potentials in the patient.Accordingly, in some embodiments, the ECU 202 can detect or receive a“probe type” input and automatically adjust the capacitance and/orresistance accordingly to allow for enhanced stimulation oramplification and detection of elicited potential. In variousembodiments, the “probe type” input can be entered manually, or thesystem can automatically detect the probe type.

In some embodiments, systems such as those herein described can beutilized for diagnostic purposes. In an exemplary procedure, such asillustrated in FIG. 7 , a probe such as those herein described can beinserted into the vasculature of a patient. In various embodiments, theprobe is inserted percutaneously, and further can be advanced into anartery (702). The probe can be used to detect signals in the arterialwall indicative of spontaneous or native activity of nerves from withinthe wall (704), for example, electrical signals. Such detected signalscan be processed in order to isolate and extract the desired spontaneoussignals (706). Processing can include averaging to eliminate temporalnoise, filtering the signal to amplify or to attenuate various frequencybands, or any other processing described herein or otherwise known inthe art.

The processed signals can be recorded (708), for example in a temporaryor permanent memory, and presented to a user for the purposes of medicaldiagnosis. Signals can be presented (710), for example, as a plot ofsignal vs. time on a display. Additionally or alternatively, the signalscan be compared to existing signal data (712) for comparing thepatient's spontaneous nerve activity to a baseline. In some examples,the patient's spontaneous nerve activity can be compared to that of ahealthy patient to assess organ or nervous health. Such a comparison canprovide indication as to whether or not ablation may be an effectivetreatment for the particular patient. In other examples, the spontaneousnervous activity can be analyzed independently from any previouslyrecorded nervous activity to determine the health of the patient'sproximate nerves or the viability of nerve treatments on the patient.

An exemplary display is shown in FIG. 8 , in which the signal is plottedagainst time, showing extracted spontaneous nerve activity proximate theartery containing the probe. Comparisons between detected nerve activityand a baseline nerve activity stored in memory can provide indicationsfor possible next steps to be performed. For instance, in some examples,if a patient displays little or no spontaneous nerve activity, aclinician may determine that a nerve destruction process is not likelyto significantly affect the patient, and may explore alternativetreatment options. In other instances, if a patient is exhibiting highlevels of abnormal nerve activity, a clinician may determine that thepatient may benefit from a nerve destruction process. As such, thediagnostic use of the probe recording electrodes can allow for theexecution of an informed treatment plan rather than the arbitrarydestruction of nerve function. Subsequently, if nerve destruction isdesired, operations such as those described above, for example as inFIG. 3 , can be carried out using the system.

Various examples of systems and methods have been described. Thedescription provided herein is exemplary in nature and is not intendedto limit the scope, applicability, or configuration of the invention inany way. Rather, the description provides practical illustrations forimplementing various exemplary embodiments. Examples of constructions,materials, dimensions, and manufacturing processes are provided forselected elements, and all other elements employ that which is known tothose of skill in the field. Those skilled in the art will recognizethat many of the examples provided have suitable alternatives that canbe utilized. These and others are within the scope of the followingclaims.

What is claimed is:
 1. A medical apparatus comprising: an electroniccontrol unit; a probe in electrical communication with the electroniccontrol unit, the probe including a plurality of electrodes located on aportion of the probe that is sized and shaped to be inserted into ablood vessel that is proximate to nerve fibers; wherein a stimulationset of one or more of the electrodes is configured to receive one ormore stimulation pulses from the electronic control unit and apply theone or more stimulation pulses to a first portion of the blood vesselproximate to the stimulation set to thereby stimulate the nerve fibersto cause an elicited response that propagates in first and seconddirections, generally opposite one another, along the nerve fibers;wherein a recording set of one or more of the electrodes is configuredto detect the elicited response of the nerve fibers that propagates, inthe first direction, from the first portion of the blood vessel towardsa second portion of the blood vessel; and wherein a blocking set of oneor more of the electrodes is configured to receive one or more blockingpulses from the electronic control unit and apply the one or moreblocking pulses to a third portion of the blood vessel proximate to theblocking set to thereby prevent at least a portion of the elicitedresponse from propagating, in the second direction, from the firstportion towards the third portion of the blood vessel.
 2. The medicalapparatus of claim 1, wherein: the electronic control unit is configuredto deliver the one or more blocking pulses to the blocking set of one ormore of the electrodes during delivery of the one or more stimulationpulses to the stimulation set of one or more of the electrodes.
 3. Themedical apparatus of claim 1, wherein: the blood vessel, which theportion of the probe is sized and shaped to be inserted into, comprisesa renal artery; and the nerve fibers, to which the one or morestimulation pulses are applied to cause the elicited response, comprisenerve fibers of renal nerves that are proximate the renal artery.
 4. Themedical apparatus of claim 1, wherein: the blood vessel supplies bloodto an organ; the recording set of one or more of the electrodes is moreproximate to the organ than the stimulation set of one or more of theelectrodes; the first direction is towards the organ; and the seconddirection is away from the organ.
 5. The medical apparatus of claim 4,wherein: the recording set of one or more of the electrodes isconfigured to detect the elicited response of the nerve fibers thatpropagates towards the organ; and the blocking set of one or more of theelectrodes is configured to apply the one or more blocking pulses to thethird portion of the blood vessel proximate to the blocking set tothereby prevent at least a portion of the elicited response frompropagating away from the organ.
 6. The medical apparatus of claim 1,wherein the one or more blocking pulses are used for at least one ofimproving patient safety or improving signal isolation.
 7. The medicalapparatus of claim 1, wherein each of the stimulation set of one or moreof the electrodes, and the blocking set of one or more of theelectrodes, is configured to deliver respective bipolar stimulation. 8.The medical apparatus of claim 1, wherein the electronic control unit isconfigured to: cause multiple separate iterations of the one or morestimulation pulses to be applied to the first portion of the bloodvessel proximate to the stimulation set, to thereby cause detection ofmultiple separate iterations of the elicited response that propagates inthe first direction; and average multiple signals indicative of themultiple separate iterations of the elicited response, to thereby reduceeffects of temporal noise that may be detected, by averaging out thetemporal noise.
 9. The medical apparatus of claim 1, wherein: at leasttwo electrodes of the stimulation set are longitudinally spaced apartfrom one another along a first segment of the probe; at least twoelectrodes of the recording set are longitudinally spaced apart from oneanother along a second segment of the probe; the second segment of theprobe is configured to be longitudinally translated relative to thefirst segment of the probe to thereby adjust a longitudinal distancebetween the at least two electrodes of the stimulation set and the atleast two electrodes of the recording set; and when the second segmentof the probe is longitudinally translated relative to the first segmentof the probe to thereby adjust the longitudinal distance between the atleast two electrodes of the recording set and the at least twoelectrodes of the stimulation set, a longitudinal distance between theat least two electrodes of the stimulation set remains unchanged, and alongitudinal distance between the at least two electrodes of recordingset remains unchanged.
 10. The medical apparatus of claim 1, wherein:one or more characteristics of one or more components of at least one ofthe electronic control unit or the probe is adjustable, the one or morecharacteristics related to at least one of a bandwidth or a resonantfrequency of the one or more components; a probe type, of the probe,affects at least one of stimulation of the nerve fibers or detection ofthe elicited response thereto; and the electronic control unit isconfigured to detect or receive an indication of the probe type, and inresponse thereto, automatically cause an adjustment to at least one ofthe one or more characteristics to improve at least one of thestimulation of the nerve fibers or the detection of the elicitedresponse thereto, compared to if the adjustment were not made.
 11. Amethod for use while a portion of a probe, including a plurality ofelectrodes, is inserted into a blood vessel that is proximate to nervefibers, the method comprising: delivering one or more stimulation pulsesto a stimulation set of one or more of the electrodes to apply the oneor more stimulation pulses to a first portion of the blood vesselproximate to the stimulation set to thereby stimulate the nerve fibersto cause an elicited response that propagates in first and seconddirections, generally opposite one another, along the nerve fibers;detecting, using a recording set of one or more of the electrodes, theelicited response of the nerve fibers that propagates, in the firstdirection, from the first portion of the blood vessel towards a secondportion of the blood vessel; and delivering one or more blocking pulsesto a blocking set of one or more of the electrodes to apply the one ormore blocking pulses to a third portion of the blood vessel proximate tothe blocking set to thereby prevent at least a portion of the elicitedresponse from propagating, in the second direction, from the firstportion towards the third portion of the blood vessel.
 12. The method ofclaim 11, wherein: the delivering the one or more blocking pulses to theblocking set of one or more of the electrodes is performed during thedelivering the one or more stimulation pulses to the stimulation set ofone or more of the electrodes.
 13. The method of claim 11, wherein: theblood vessel, which the portion of the probe is sized and shaped to beinserted into, comprises a renal artery; and the nerve fibers, to whichthe one or more stimulation pulses are applied to cause the elicitedresponse, comprise nerve fibers of renal nerves that are proximate therenal artery.
 14. The method of claim 11, wherein: the blood vesselsupplies blood to an organ; the recording set of one or more of theelectrodes is more proximate to the organ than the stimulation set ofone or more of the electrodes; the first direction is towards the organ;and the second direction is away from the organ.
 15. The method of claim14, wherein: the recording set of one or more of the electrodes detectsthe elicited response of the nerve fibers that propagates towards theorgan; and the blocking set of one or more of the electrodes applies theone or more blocking pulses to the third portion of the blood vesselproximate to the blocking set to thereby prevent at least a portion ofthe elicited response from propagating away from the organ.
 16. Themethod of claim 11, wherein the one or more blocking pulses are used forat least one of improving patient safety or improving signal isolation.17. The method of claim 11, wherein each of the stimulation set of oneor more of the electrodes, and the blocking set of one or more of theelectrodes delivers respective bipolar stimulation.
 18. The method ofclaim 11, further comprising: causing multiple separate iterations ofthe delivering the one or more stimulation pulses and the detecting theelicited response thereto; and averaging multiple signals indicative ofthe multiple separate iterations of the elicited response that aredetected, to thereby reduce effects of temporal noise that may bedetected, by averaging out the temporal noise.
 19. The method of claim11, wherein: at least two electrodes of the stimulation set arelongitudinally spaced apart from one another along a first segment ofthe probe; and at least two electrodes of the recording set arelongitudinally spaced apart from one another along a second segment ofthe probe; the second segment of the probe is configured to belongitudinally translated relative to the first segment of the probe tothereby adjust a longitudinal distance between the at least twoelectrodes of the stimulation set and the at least two electrodes of therecording set; and further comprising longitudinally translating thesecond segment of the probe relative to the first segment of the probeto thereby adjust the longitudinal distance between the recording setand the stimulation set, without changing a longitudinal distancebetween the at least two electrodes of the stimulation set, and withoutchanging a longitudinal distance between the at least two electrodes ofrecording set.
 20. The method of claim 11, wherein: one or morecharacteristics of one or more components of at least one of the probeor an electronic control unit to which the probe is electricallycoupled, is/are adjustable, the one or more characteristics related toat least one of a bandwidth or a resonant frequency of the one or morecomponents; a probe type, of the probe, affects at least one ofstimulation of the nerve fibers or detection of the elicited responsethereto; and further comprising detecting or receiving an indication ofthe probe type, and in response thereto, automatically adjusting atleast one of the one or more characteristics to improve at least one ofthe stimulation of the nerve fibers or the detection of the elicitedresponse thereto, compared to if the adjusting was not performed.